Novel oxidation of substituted pyrrolidines by n-bromosuccinimide; Rapid synthesis of pyrrolo[2,1-α]isoquinolines

Article abstract of DOI:10.1055/s-0029-1217063

A new method for converting 1,2,3,5,6,10b-hexahydropyrrolo[2,1-α] isoquinolines into 5,6-dihydropyrrolo[2,1-a]isoquinolines by the use of N-bromosuccinimide as an oxidant is presented. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1217063

PAPER
4149
Novel Oxidation of Substituted Pyrrolidines by N-Bromosuccinimide; Rapid
Synthesis of Pyrrolo[2,1-a]isoquinolines
O
xidation
u
of Pyrrolidin
d
es by
N
-Bro
i
mosuc
t
cinimide Tóth,a Linda Váradi,a András Dancsó,b Gábor Blaskó,b,1 László Tőke,a Miklós Nyerges*a,1
a
Organic Chemical Technology Research Group of the Hungarian Academy of Sciences,
Budapest University of Technology and Economics, P.O.B. 91, 1521 Budapest, Hungary
E-mail: miklos.nyerges@hu.netgrs.com
EGIS Pharmaceuticals Ltd., P.O.B. 100, 1475 Budapest, Hungary
Fax +36(1)8812011
b
Received 22 July 2009
duced by dehydrohalogenation reacted with a wide range
of dipolarophiles e.g. maleimides, maleates, nitro olefins
etc. Accordingly, the reaction of 1 with methyl bromo-
acetate or phenacyl bromides, in anhydrous diethyl ether,
gave the quaternary salts 2. Reaction of isoquinolinium
salts 2 with triethylamine at ambient temperature in the
presence of the appropriate dipolarophiles 3 gave stereo-
selectively the corresponding anti-endo cycloadducts 4 in
high yield (Scheme 1). Alternatively, several of these cy-
cloadducts could be prepared directly from 1 using a one-
step method described by us (for characterization see
Table 2).13g
Abstract: A new method for converting 1,2,3,5,6,10b-hexahydro-
pyrrolo[2,1-a]isoquinolines into 5,6-dihydropyrrolo[2,1-a]isoquin-
olines by the use of N-bromosuccinimide as an oxidant is presented.
Key words: azomethine ylides, cycloadditions, oxidation, pyrroles
The biological importance of pyrrole-containing natural
products, such as heme, chlorophyll, and vitamin B12 and
a large number of alkaloids has stimulated extensive re-
search on the synthesis and reactivity of pyrrole deriva-
tives.2 There are many methods for the synthesis of these
important heterocycles, including the 1,3-dipolar cycload-
dition of azomethine ylides to alkynes, followed by arom-
atization of the intermediate pyrrolines.3 However, the
preparation of pyrroles by dehydrogenation of pyrro-
lidines has found little application due to lack of general
methods and the forcing conditions required in most
cases.4
MeO
MeO
MeO
MeO
Br–
N+
EWG
i.
N
2
1
MeO
ii.
N
The development of a method that allows this reaction un-
der essentially mild and neutral conditions should height-
en the synthetic potential of this conversion. In this paper
we report our results on the direct conversion of one type
of pyrrolidine into the corresponding pyrrole in excellent
yields using N-bromosuccinimide under mild conditions.5
Ar
EWG
MeO
NO2
H
3
O2N
Ar
4
Scheme 1 Reagents and conditions: (i) EWG-CH2Br, Et2O, r.t.; (ii)
Et3N, EtOH, r.t.
Considerable interest has been shown in substituted pyr-
rolo[2,1-a]isoquinolines due to their diverse biological
activity. Since the discovery of the potent cytotoxic and
topoisomerase I inhibitor activity of lamellarine alka-
loids,6 a number of new synthetic strategies have been de-
veloped based on, e.g. intramolecular oxidative biaryl
coupling,7 thermal reactions of 4-isoxazoline derivatives
(obtained by cycloaddition of 3,4-dihydroisoquinoline N-
oxides with alkynes),8 intramolecular Heck reactions,9
and cyclization of 1- or 2-benzylisoquinolines.10,11
After several unsuccessful exploratory experiment using
various oxidizing agents (e.g., MnO2, DDQ, H2O2,
KMnO4) we decided to use N-bromosuccinimide,14 which
is most frequently used for the oxidation of sulfides to
sulfoxides15 and alcohols to carbonyl compounds.16 This
reagent was useful for the direct transformation of alde-
hydes into acid bromides17 or nitriles.18 However, there
are few reports on the oxidation of heterocyclic com-
pounds with N-bromosuccinimide; the oxidation of in-
As a continuation of our research programme in this
field12 we have decided to study the dehydrogenation of
1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolines 4,
which were prepared by 1,3-dipolar cycloaddition of
azomethine ylides derived from dihydroisoquinolinium
salts previously studied in detail by us.13 The dipoles pro-
doles
to
isatins,19
2,3-dihydrobenzofurans
to
benzofurans,20 and isoxazoline to isoxazole21 has been ac-
complished by N-bromosuccinimide. In addition to some
two-step processes (halogenation with NBS; dehydroha-
logenation by a base),22 in one case a 3,4-dihydroisoquin-
oline derivative was aromatized in refluxing carbon
tetrachloride in the presence of N-bromosuccinimide.23
SYNTHESIS 2009, No. 24, pp 4149–4158
x
x.
x
x
.
2
0
0
9
Advanced online publication: 19.10.2009
DOI: 10.1055/s-0029-1217063; Art ID: P10409SS
© Georg Thieme Verlag Stuttgart · New York

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J. Tóth et al.
PAPER
Table 1 5,6-Dihydropyrrolo[2,1-a]isoquinolines 5 Obtained
Entry
1
Cycloadducta EWG
Ar
Temp
r.t.
Productb
Yield (%)
MeO
MeO
N
CO2Me
4a13g
CO2Me
5a
72
70
O2N
MeO
MeO
N
CO2Me
2
3
4
5
4b13g
CO2Me
CO2Me
CO2Me
CO2Me
r.t.
5b
5c
5d
5e
O2N
OMe
OMe
MeO
MeO
N
N
N
CO2Me
MeO
MeO
4c13g
4d13g
4e13g
0 °C
81
77
60
O2N
OMe
OMe
MeO
MeO
CO2Me
MeO
MeO
0 °C
to r.t.
O2N
Br
OMe
OMe
MeO
MeO
MeO
MeO
CO2Me
0 °C
O2N
Br
OMe
OMe
MeO
N
OMe
MeO
MeO
CO2Me
6
7
4f13g
CO2Me
r.t.
r.t.
5f
81
86
O2N
NO2
NO2
MeO
MeO
N
CO2Me
N
4g13g
CO2Me
5g
O2N
N
Synthesis 2009, No. 24, 4149–4158 © Thieme Stuttgart · New York

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Oxidation of Substituted Pyrrolidines by N-Bromosuccinimide
4151
Table 1 5,6-Dihydropyrrolo[2,1-a]isoquinolines 5 Obtained (continued)
Entry
Cycloadducta EWG
Ar
Temp
r.t.
Productb
Yield (%)
MeO
MeO
N
CO2Me
4h
(69%)
5h
8
CO2Me
78
85
63
O2N
BnO
OBn
MeO
MeO
N
COPh
9
4i13g
COPh
COPh
r.t.
r.t.
5i
5j
O2N
NO2
NO2
MeO
MeO
N
COPh
4j
(75%)
10
O2N
Cl
Cl
MeO
MeO
N
N
N
COPh
Cl
4k
(69%)
11
12
COPh
r.t.
r.t.
5k
58
77
O2N
O2N
O2N
Cl
MeO
MeO
O
4l
(70%)
4-MeOC6H4CO
5l
OMe
MeO
MeO
O
4m
(70%)
13
4-MeOC6H4CO
r.t.
5m
68
Cl
OMe
Cl
O
MeO
MeO
N
4n
(58%)
14
4-MeOC6H4CO
r.t.
5n
54
O2N
Cl
Cl
OMe
Br
Cl
Cl
Synthesis 2009, No. 24, 4149–4158 © Thieme Stuttgart · New York

4152
J. Tóth et al.
PAPER
Table 1 5,6-Dihydropyrrolo[2,1-a]isoquinolines 5 Obtained (continued)
Entry
15
Cycloadducta EWG
Ar
Temp
r.t.
Productb
Yield (%)
MeO
MeO
O
O
O
N
N
N
4o
(77%)
5o
4-BrC6H4CO
65
59
O2N
O2N
O2N
Br
Br
Br
MeO
MeO
4p
(73%)
16
17
4-BrC6H4CO
r.t.
5p
5q
Cl
Cl
MeO
MeO
O
4q
(84%)
0 °C
to r.t.
4-BrC6H4CO
53
O
Br
O
O
a Where the cycloadduct is new, the yield has been given and spectroscopic data are given in Table 2.
b Spectroscopic data are given in Table 3.
c NBS (3 equiv) was used.
To our delight, we found that on treatment with N-bromo- The structures of compound 5 were elucidated by NMR
1
1
1
succinimide at room temperature the colorless solution of spectroscopy using H, 13C, H–1H COSY, H–1H NOE,
4 in chloroform immediately became yellow and, after a and 1H–13C HSQC techniques (Table 3).
simple workup procedure, the desired 5,6-dihydropyrro-
lo[2,1-a]isoquinolines 5 were obtained (Scheme 2).
The mechanism of oxidation of pyrrolidines 4 with N-bro-
mosuccinimide has not been clearly established, although
based on the earlier interpretations it is generally accepted
MeO
MeO
i.
that a positive halogen is the attacking species giving a
brominated intermediate.14 The spontaneous elimination
of hydrogen bromide occurs facilitated by the high conju-
gation of the newly formed double bond. We believe that
the pyrrolidines 4 reacts with N-bromosuccinimide to
form pyrroline 6 exclusively accordingly to path A. The
formation of isomeric pyrroline 7 is unlikely because that
would readily lose nitrous acid to form a different pyrrole
N
N
EWG
EWG
MeO
MeO
H
O2N
O2N
Ar
Ar
5
4
Scheme 2 Reagents and conditions: (i) NBS, CHCl3, r.t.
The reaction is exothermic and on a larger scale, external 8 as the product.4e The last step is a spontaneous dehydro-
ice-water cooling is necessary. To demonstrate the gener- genation leading to the formation of the isolated pyrroles
ality of this methodology, a broad range of different cy- 5 (Scheme 3).12
cloadducts were chosen to explore the scope of this
In summary we have explored a convenient two-step reac-
approach. The results are summarized in Table 1. In gen-
tion path which provides a useful route to 5,6-dihydro-
eral, modest to good overall yields were obtained for all
pyrrolo[2,1-a]isoquinolines 5 via a 1,3-dipolar cyclo-
addition; N-bromosuccinimide-promoted oxidation se-
quence. The obtained new pyrrolo[2,1-a]isoquinoline de-
rivatives 5 could be useful intermediates in the synthesis
substrates. A limitation of this method is that in cases
when the aromatic ring has two or more electron-donating
substituents (Table 1, entries 4, 5, 14, and 17) the concom-
itant bromination of the 2-aryl substituent was observed
of lamellarine-type heterocycles through a standard NO2
concurring with the dehydrogenation process, which can
to Br functional group exchange followed by a Suzuki
be avoided applying a lower reaction temperature.
coupling with arylboronic acid derivatives, which is well
established in this series.24 These studies are in progress in
our laboratories.
Synthesis 2009, No. 24, 4149–4158 © Thieme Stuttgart · New York

PAPER
Oxidation of Substituted Pyrrolidines by N-Bromosuccinimide
4153
MeO
'O'
MeO
MeO
path A
N
N
EWG
EWG
MeO
O2N
O2N
Ar
Ar
4
6
5
MeO
MeO
MeO
MeO
path B
– HNO2
N
N
EWG
EWG
O2N
Ar
Ar
8
7
Scheme 3
Table 2 Spectral Data of Compounds 4 Prepared
Product IR (KBr, cm–1) 1H NMRa (CDCl3, TMS) d
4h 2936, 2907, 2843, 2803,
13C NMR (CDCl3, TMS) d
7.38 (m, 5 H, HBn), 7.24 (d, J = 8.7 Hz, 2 H, H2¢, H6¢), 171.3 (Cq), 158.4 (Cq), 147.4 (Cq), 136.7 (Cq),
6.94 (d, J = 8.7 Hz, 2 H, H3¢, H5¢), 6.61 (s, 1 H, H7), 129.8 (Cq), 129.1 (2 CH), 128.6 (2 CH), 128.5
6.52 (s, 1 H, H10), 5.55 (dd, J = 3.5, 7.1 Hz, 1 H, H1), (CH), 128.0 (Cq), 127.4 (2 CH), 115.2 (2 CH),
5.37 (d, J = 7.1 Hz, 1 H, H10b), 5.04 (s, 2 H, OCH2), 114.8 (Cq), 111.4 (CH), 109.1 (CH), 95.6 (CH),
4.51 (d, J = 7.8 Hz, 1 H, H3), 4.36 (dd, J = 3.5, 7.8 Hz, 70.3 (CH), 70.0 (CH2), 64.0 (CH), 55.9 (CH3),
1 H, H2), 3.84 (s, 3 H, OMe), 3.81 (s, 3 H, OMe), 3.39 55.7 (CH3), 51.6 (CH3), 51.4 (CH), 46.1 (CH2),
1748, 1611, 1548, 1518,
1462, 1383, 1364, 1317,
1273, 1244, 1227, 1145,
1106, 1090, 1044, 1020
(s, 3 H, OMe), 3.30 (m, 1 H, H5), 2.85 (m, 1 H, H5),
2.65 (m, 2 H, H6)
26.7 (CH2)
4j
2918, 2849, 1671, 1611,
1545, 1521, 1495, 1369,
1275, 1263, 1232, 1137,
1121, 1096, 1014
7.86 (d, J = 7.4 Hz, 2 H, H2¢¢, H6¢¢), 7.61 (d, J = 7.4
196.6 (Cq), 147.9 (Cq), 146.9 (Cq), 136.3 (Cq),
Hz, 2 H, H3¢¢, H5¢¢), 7.48 (t, J = 7.4 Hz, 1 H, H4¢¢), 7.33 136.0 (Cq), 133.5 (Cq), 131.8 (Cq), 129.9 (2
(d, J = 8.2 Hz, 2 H, H2¢, H6¢), 7.31 (d, J = 8.2 Hz, 2 H, CH), 128.9 (2 CH), 128.5 (2 CH), 128.3 (2
H3¢, H5¢), 6.91 (s, 1 H, H7), 6.74 (s, 1 H, H10), 6.12 CH), 127.9 (CH), 122.9 (Cq), 111.6 (CH),
(t, J = 6.5 Hz, 1 H, H1), 5.82 (d, J = 6.5 Hz, 1 H, H3), 110.7 (CH), 95.9 (CH), 71.6 (CH), 63.7 (CH),
5.13 (d, J = 6.5 Hz, 1 H, H10b), 4.74 (t, J = 6.5 Hz, 1 55.7 (CH3), 55.5 (CH3), 50.7 (CH), 46.1 (CH2),
H, H2), 3.75 (s, 3 H, OMe), 3.70 (s, 3 H, OMe), 3.39
(m, 1 H, H5), 3.22 (m, 1 H, H5), 2.81 (m, 1 H, H6),
2.68 (m, 1 H, H6)
27.5 (CH2)
4k
2955, 2926, 2872, 2837,
1677, 1579, 1550, 1519,
1478, 1463, 1447, 1386,
1370, 1349, 1326, 1290,
1270, 1137, 1118, 1090,
1037, 1010
7.74 (d, J = 7.4 Hz, 2 H, H2¢¢, H6¢¢), 7.65 (d, J = 8.0
197.0 (Cq), 148.2 (Cq), 147.4 (Cq), 136.4 (Cq),
Hz, 1 H, H6¢), 7.47 (t, J = 7.4 Hz, 1 H, H4¢¢), 7.35 (d, 133.8 (Cq), 133.2 (CH), 132.8 (Cq), 129.6
J = 7.4 Hz, 2 H, H3¢¢, H5¢¢), 7.22 (t, J = 8.0 Hz, 1 H,
H5¢), 7.18 (d, J = 8.0 Hz, 1 H, H3¢), 7.09 (t, J = 8.0 Hz, 128.1 (Cq), 127.9 (2 CH), 127.3 (CH), 122.3
1 H, H4¢), 6.62 (s, 1 H, H7), 6.56 (s, 1 H, H10), 5.88 (Cq), 111.3 (CH), 109.3 (CH), 95.1 (CH), 71.1
(dd, J = 5.3, 7.5 Hz, 1 H, H1), 5.66 (d, J = 7.3 Hz, 1 H, (CH), 63.7 (CH), 55.9 (CH3), 55.7 (CH3), 48.6
H3), 5.28 (d, J = 7.5 Hz, 1 H, H10b), 5.08 (dd, J = 5.3, (CH), 46.8 (CH2), 27.5 (CH2)
7.3 Hz, 1 H, H2), 3.85 (s, 3 H, OMe), 3.83 (s, 3 H,
(CH), 129.4 (CH), 128.9 (CH), 128.5 (2 CH),
OMe), 3.52 (m, 1 H, H5), 3.28 (m, 1 H, H5), 2.90 (m,
1 H, H6), 2.80 (m, 1 H, H6)
4l
3006, 2942, 2839, 1666,
1602, 1576, 1549, 1522,
1467, 1443, 1423, 1368,
1317, 1266, 1232, 1182,
1134, 1115, 1057, 1025
7.87 (d, J = 8.7 Hz, 2 H, H2¢¢, H6¢¢), 7.28 (d, J = 7.7
194.8 (Cq), 163.4 (Cq), 147.8 (Cq), 146.8 (Cq),
Hz, 2 H, H2¢, H6¢), 7.22 (d, J = 7.7 Hz, 2 H, H3¢, H5¢), 137.0 (Cq), 130.8 (2 CH), 129.3 (Cq), 128.5 (2
7.13 (t, J = 7.7 Hz, 1 H, H4¢), 6.96 (d, J = 8.7 Hz, 2 H, CH), 127.8 (2 CH), 127.6 (CH), 127.0 (Cq),
H3¢¢, H5¢¢), 6.89 (s, 1 H, H7), 6.72 (s, 1 H, H10), 6.18 123.0 (Cq), 114.0 (2 CH), 111.5 (CH), 110.6
(t, J = 7.0 Hz, 1 H, H1), 5.77 (d, J = 7.0 Hz, 1 H, H3), (CH), 96.3 (CH), 71.2 (CH), 63.9 (CH), 55.7
5.13 (d, J = 7.0 Hz, 1 H, H10b), 4.69 (t, J = 7.0 Hz, 1 (CH3), 55.6 (CH3), 55.5 (CH3), 51.5 (CH), 46.3
H, H2), 3.81 (s, 3 H, OMe), 3.72 (s, 3 H, OMe), 3.68
(s, 3 H, OMe), 3.39 (m, 1 H, H5), 3.21 (m, 1 H, H5),
2.79 (m, 1 H, H6), 2.70 (m, 1 H, H6)
(CH2), 27.9 (CH2)
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Table 2 Spectral Data of Compounds 4 Prepared (continued)
Product IR (KBr, cm–1)
3003, 2932, 2867, 2841,
1H NMRa (CDCl3, TMS) d
13C NMR (CDCl3, TMS) d
194.4 (Cq), 163.7 (Cq), 148.2 (Cq), 147.3 (Cq),
4m
4n
4o
7.80 (d, J = 7.0 Hz, 2 H, H2¢¢, H6¢¢), 7.18 (d, J = 8.6
1658, 1601, 1550, 1519,
1495, 1462, 1365, 1342,
1320, 1269, 1239, 1179,
1131, 1118, 1097, 1024,
1017
Hz, 2 H, H2¢, H6¢), 7.11 (d, J = 8.6 Hz, 2 H, H3¢¢, H5¢¢), 134.6 (Cq), 133.3 (Cq), 130.4 (2 CH), 129.4
6.87 (d, J = 7.0 Hz, 2 H, H3¢, H5¢), 6.61 (s, 1 H, H7), (Cq), 129.2 (2 CH), 128.9 (2 CH), 128.1 (Cq),
6.54 (s, 1 H, H10), 5.80 (dd, J = 4.8, 7.6 Hz, 1 H, H1), 122.4 (Cq), 113.9 (2 CH), 111.2 (CH), 109.3
5.50 (d, J = 7.1 Hz, 1 H, H3), 5.24 (d, J = 7.6 Hz, 1 H, (CH), 91.2 (CH), 71.4 (CH), 63.9 (CH), 55.9
H10b), 4.48 (dd, J = 4.8, 7.1 Hz, 1 H, H2), 3.85 (s, 3
(CH3), 55.7 (CH3), 55.5 (CH3), 51.7 (CH), 46.6
H, OMe), 3.84 (s, 3 H, OMe), 3.83 (s, 3 H, OMe), 3.45 (CH2), 27.1 (CH2)
(m, 1 H, H5), 3.26 (m, 1 H, H5), 2.86 (m, 1 H, H6),
2.75 (m, 1 H, H6)
2935, 2838, 1662, 1600,
1572, 1550, 1519, 1464,
1424, 1386, 1366, 1270,
1233, 1176, 1138, 1119,
1024
7.79 (d, J = 7.0 Hz, 2 H, H2¢¢, H6¢¢), 7.63 (d, J = 8.5
194.8 (Cq), 163.8 (Cq), 148.2 (Cq), 147.3 (Cq),
Hz, 1 H, H6¢), 7.23 (d, J = 2.1 Hz, 1 H, H3¢), 7.20 (dd, 134.4 (Cq), 134.0 (Cq), 131.6 (Cq), 130.45 (2
J = 2.1, 8.5 Hz, 1 H, H5¢), 6.86 (d, J = 7.0 Hz, 2 H,
CH), 130.4 (CH), 129.3 (CH), 129.0 (Cq),
H3¢¢, H5¢¢), 6.61 (s, 1 H, H7), 6.55 (s, 1 H, H10), 5.90 127.9 (Cq), 127.5 (CH), 122.1 (Cq), 113.8 (2
(dd, J = 5.6, 7.6 Hz, 1 H, H1), 5.59 (d, J = 7.1 Hz, 1 H, CH), 111.2 (CH), 109.2 (CH), 95.1 (CH), 70.4
H3), 5.25 (d, J = 7.6 Hz, 1 H, H10b), 5.00 (dd, J = 5.6, (CH), 63.6 (CH), 55.9 (CH3), 55.7 (CH3), 55.4
7.1 Hz, 1 H, H2), 3.84 (s, 3 H, OMe), 3.83 (s, 3 H,
OMe), 3.82 (s, 3 H, OMe), 3.51 (m, 1 H, H5), 3.26 (m,
1 H, H5), 2.86 (m, 2 H, H6)
(CH3), 48.3 (CH), 46.8 (CH2), 27.5 (CH2)
2934, 2836, 1676, 1612,
1584, 1547, 1520, 1465,
1405, 1366, 1339, 1318,
1273, 1231, 1135, 1120,
1073, 1010
7.71 (d, J = 8.5 Hz, 2 H, H2¢¢, H6¢¢), 7.60 (d, J = 8.5
196.1 (Cq), 147.8 (Cq), 146.9 (Cq), 136.8 (Cq),
Hz, 2 H, H3¢¢, H5¢¢), 7.22 (d, J = 7.5 Hz, 2 H, H2¢, H6¢), 135.4 (Cq), 131.8 (2 CH), 130.3 (2 CH), 128.6
7.18 (d, J = 7.5 Hz, 2 H, H3¢, H5¢), 7.10 (t, J = 7.5 Hz, (2 CH), 128.0 (2 CH), 127.9 (CH), 127.5 (Cq),
1 H, H4¢), 6.87 (s, 1 H, H7), 6.69 (s, 1 H, H10), 6.05
127.2 (Cq), 123.0 (Cq), 111.6 (CH), 110.7
(dd, J = 5.6, 7.2 Hz, 1 H, H1), 5.74 (d, J = 7.4 Hz, 1 H, (CH), 96.0 (CH), 71.7 (CH), 63.8 (CH), 55.7
H3), 5.09 (d, J = 7.2 Hz, 1 H, H10b), 4.66 (dd, J = 5.6, (CH3), 55.5 (CH3), 51.4 (CH), 46.1 (CH2), 27.6
7.4 Hz, 1 H, H2), 3.69 (s, 3 H, OMe), 3.64 (s, 3 H,
OMe), 3.55 (m, 1 H, H5), 3.18 (m, 1 H, H5), 2.78 (m,
1 H, H6), 2.66 (m, 1 H, H6)
(CH2)
4p
4q
2908, 2833, 1671, 1582,
1553, 1524, 1480, 1468,
1399, 1376, 1289, 1259,
1232, 1216, 1180, 1154,
1119, 1071, 1054, 1040,
1015, 1009
7.62 (m, 3 H, H6¢, H2¢¢, H6¢¢), 7.49 (m, 3 H, H5¢, H3¢¢, 196.1 (Cq), 148.2 (Cq), 147.3 (Cq), 135.0 (Cq),
H5¢¢), 7.21 (d, J = 7.7 Hz, 1 H, H3¢), 7.11 (d, J = 7.7
Hz, 1 H, H4¢), 6.62 (s, 1 H, H10), 6.56 (s, 1 H, H7),
133.7 (Cq), 132.6 (CH), 131.8 (2 CH), 129.3
(CH), 129.1 (Cq), 128.4 (Cq), 128.1 (Cq), 127.3
5.85 (dd, J = 5.1, 7.5 Hz, 1 H, H1), 5.60 (d, J = 7.3 Hz, (CH), 122.1 (Cq), 111.2 (CH), 109.3 (CH), 94.9
1 H, H3), 5.27 (d, J = 7.5 Hz, 1 H, H10b), 5.06 (dd, J = (CH), 71.0 (CH), 63.6 (CH), 55.9 (CH3), 55.7
5.1, 7.3 Hz, 1 H, H2), 3.85 (s, 3 H, OMe), 3.82 (s, 3 H, (CH3), 48.5 (CH), 46.8 (CH2), 27.4 (CH2)
OMe), 3.50 (m, 1 H, H5), 3.29 (m, 1 H, H5), 2.91 (m,
1 H, H6), 2.80 (m, 1 H, H6)
3002, 2937, 2835, 1733,
1653, 1611, 1546, 1514,
1465, 1365, 1232, 1179,
1136, 1119, 1013
7.64 (d, J = 8.6 Hz, 2 H, H2¢¢, H6¢¢), 7.51 (d, J = 8.6
195.8 (Cq), 148.2 (Cq), 148.0 (Cq), 147.4 (Cq),
Hz, 2 H, H3¢¢, H5¢¢), 6.69 (s, 1 H, H7), 6.61 (d, J = 8.1 147.1 (Cq), 139.1 (Cq), 135.5 (Cq), 131.9 (2
Hz, 1 H, H5¢), 6.57 (d, J = 8.1 Hz, 1 H, H6¢), 6.53 (s, 1 CH), 129.4 (2 CH), 128.4 (Cq), 126.6 (Cq),
H, H2¢), 6.06 (s, 1 H, H10), 5.89 (s, 2 H, OCH2O), 5.63 122.5 (Cq), 121.6 (CH), 111.3 (CH), 109.3
(dd, J = 3.9, 7.3 Hz, 1 H, H1), 5.46 (d, J = 7.2 Hz, 1 H, (CH), 108.42 (CH), 108.40 (CH), 101.2 (CH2),
H3), 5.28 (d, J = 7.3 Hz, 1 H, H10b), 4.36 (dd, J = 3.9, 96.3 (CH), 71.8 (CH), 63.8 (CH), 55.9 (CH3),
7.2 Hz, 1 H, H2), 3.85 (s, 3 H, OMe), 3.82 (s, 3 H,
OMe), 3.40 (m, 1 H, H5), 3.26 (m, 1 H, H5), 2.88 (m,
1 H, H6), 2.70 (m, 1 H, H6)
55.7 (CH3), 52.1 (CH), 46.5 (CH2), 26.7 (CH2)
a Aryl groups at C2 are indicated using ¢, while those at C3 are indicated by ¢¢.
given in Table 1. The solution immediately turned yellow. The mix-
ture was stirred for 30 min and then H2O (10 mL) was added and the
organic layer was washed with further portions of H2O (2 × 10 mL)
and brine (10 mL), dried (MgSO4), and evaporated in vacuo. The
residue was triturated with cold EtOH and filtered to yield the title
products as yellow powders.
IR spectra were measured on a Bruker Vector 22 FT-IR instrument.
NMR spectra were recorded on a Bruker Avance DRX-500 spec-
trometer relative to TMS. All solvents were purified according to
standard procedures.
5,6-Dihydropyrrolo[2,1-a]isoquinoline-3-carboxylates 5a–l;
General Procedure
The cycloadduct 4 (1.0 mmol) was dissolved in CHCl3 (10 mL) and
NBS (0.17 g, 1.1 mmol) was added in 1 portion at the temperature
Synthesis 2009, No. 24, 4149–4158 © Thieme Stuttgart · New York

PAPER
Oxidation of Substituted Pyrrolidines by N-Bromosuccinimide
1H NMRa (CDCl3, TMS) d, J (Hz) 13C NMR (CDCl3,TMS) d
4155
Table 3 Spectral Data of Compounds 5 Prepared
Product IR (KBr, cm–1)
5a
5b
5c
2956, 2833, 1700, 1609,
7.39 (m, 4 H, HPh, H10), 7.29 (m, 2 H, HPh), 6.79 (s, 161.3 (Cq), 150.2 (Cq), 147.9 (Cq), 136.4 (Cq),
1 H, H7), 4.58 (t, J = 6.7 Hz, 2 H, H5), 3.94 (s, 3 H, 132.3 (Cq), 130.9 (Cq), 129.6 (Cq), 129.5 (2 CH),
OMe), 3.86 (s, 3 H, OMe), 3.53 (s, 3 H, OMe), 3.06 128.1 (Cq), 127.8 (CH), 127.6 (2 CH), 117.2 (Cq),
1591, 1561, 1547, 1506,
1452, 1439, 1355, 1284,
1262, 1236, 1217, 1195,
1181, 1136, 1100, 1072,
1016
(t, J = 6.7 Hz, 2 H, H6)
114.7 (Cq), 110.5 (CH), 109.9 (CH), 56.5 (CH3),
56.0 (CH3), 51.4 (CH3), 43.0 (CH2), 28.8 (CH2)
3000, 2939, 2845, 1680,
1499, 1310, 1287, 1175,
1142, 1133, 1097, 1011
7.21 (s, 1 H, H10), 7.16 (d, J = 8.8 Hz, 2 H, H2¢,
6¢H), 7.05 (s, 1 H, H7), 6.92 (d, J = 8.8, 2 H, H3¢,
H5¢), 4.45 (t, J = 5.6 Hz, 2 H, H5), 3.83 (s, 3 H,
160.9 (Cq), 159.1 (Cq), 155.2 (Cq), 150.6 (Cq),
147.6 (Cq), 130.8 (2 CH), 130.5 (Cq), 129.1 (Cq),
129.0 (Cq), 124.3 (Cq), 119.0 (Cq), 116.8 (Cq),
OMe), 3.79 (s, 3 H, OMe), 3.70 (s, 3 H, OMe), 3.51 113.6 (2 CH), 111.8 (CH), 110.2 (CH), 56.6
(s, 3 H, OMe), 3.04 (t, J = 6.7 Hz, 2 H, H6)
(CH3), 56.1 (CH3), 55.5 (CH3), 52.0 (CH3), 43.3
(CH2), 28.2 (CH2)
2932, 1697, 1560, 1531,
1502, 1463, 1422, 1373,
1320, 1232, 1175, 1122
7.22 (s, 1 H, H10), 6.91 (d, J = 8.3 Hz, 1 H, H5¢),
161.8 (Cq), 159.2 (Cq), 149.0 (Cq), 148.5 (Cq),
6.85 (s, 1 H, H2¢), 6.74 (d, J = 8.3 Hz, 1 H, H6¢), 6.72 146.7 (Cq), 137.3 (Cq), 133.1 (Cq), 131.6 (Cq),
(s, 1 H, H7), 4.45 (t, J = 5.5 Hz, 2 H, H5), 3.96 (s, 3 129.5 (Cq), 129.1 (Cq), 128.5 (Cq), 124.9 (Cq),
H, OMe), 3.88 (s, 3 H, OMe), 3.82 (s, 3 H, OMe),
120.1 (CH), 115.4 (CH), 114.2 (CH), 112.9
3.79 (s, 3 H, OMe), 3.56 (s, 3 H, OMe), 3.02 (t, J = (CH), 112.4 (CH), 59.2 (CH3), 58.9 (CH3), 56.6
5.5 Hz, 2 H, H6)
(CH3), 56.3 (CH3), 52.0 (CH3), 44.2 (CH2), 28.2
(CH2)
5d
5e
2956, 1685, 1610, 1532,
1462, 1372, 1275, 1210,
1170, 1132, 1011
7.20 (s, 1 H, H10), 6.86 (s, 1 H, H6¢), 6.72 (s, 1 H,
166.1 (Cq), 150.3 (Cq), 148.1 (Cq), 146.3 (Cq),
H2¢), 6.79 (s, 1 H, H7), 4.40 (t, J = 5.5 Hz, 2 H, H5), 136.2 (Cq), 134.8 (Cq), 133.7 (Cq), 131.5 (Cq),
3.89 (s, 3 H, OMe), 3.85 (s, 3 H, OMe), 3.83 (s, 3 H, 130.1 (Cq), 129.1 (Cq), 127.9 (Cq), 123.6 (Cq),
OMe), 3.79 (s, 3 H, OMe), 3.54 (s, 3 H, OMe), 3.03 117.9 (CH), 116.4 (CH), 115.7 (CH), 115.1 (Cq),
(t, J = 5.5 Hz, 2 H, H6)
114.5 (CH), 59.1 (CH3), 59.3 (CH3), 56.7 (CH3),
56.5 (CH3), 56.1 (CH3), 43.4 (CH2), 28.1 (CH2)
2993, 2940, 2840, 1709,
1669, 1563, 1505, 1475,
1443, 1427, 1387, 1343,
1301, 1287, 1260, 1214,
1195, 1138, 1107, 1049,
1013
7.49 (s, 1 H, H10), 6.79 (s, 1 H, H7), 6.63 (s, 1 H,
160.9 (Cq), 152.2 (Cq), 150.7 (Cq), 150.4 (Cq),
H6¢), 4.61 (m, 2 H, H5), 3.96 (s, 3 H, OMe), 3.95 (s, 147.7 (Cq), 142.5 (Cq), 131.6 (Cq), 131.5 (Cq),
3 H, OMe), 3.93 (s, 3 H, OMe), 3.89 (s, 3 H, OMe), 129.7 (Cq), 128.0 (Cq), 127.4 (Cq), 118.6 (Cq),
3.83 (s, 3 H, OMe), 3.34 (s, 3 H, OMe), 3.06 (m, 2 H, 117.1 (Cq), 111.0 (Cq), 110.5 (CH), 110.4 (CH),
H6)
109.8 (CH), 61.2 (CH3), 61.0 (CH3), 56.13
(CH3), 56.12 (CH3), 56.0 (CH3), 51.7 (CH3), 43.0
(CH2), 28.8 (CH2)
5f
2956, 1708, 1581, 1521,
1502, 1472, 1456, 1442,
1395, 1350, 1262, 1216,
1197, 1143
8.26 (d, J = 7.7 Hz, 1 H, H6¢), 8.17 (s, 1 H, H2¢), 7.77 160.1 (Cq), 150.6 (Cq), 147.4 (Cq), 147.2 (Cq),
(d, J = 7.7 Hz, 1 H, H4¢), 7.71 (t, J = 7.7 Hz, 1 H, 136.6 (CH), 134.7 (Cq), 131.7 (CH), 130.8 (Cq),
H5¢), 7.39 (s, 1 H, H10), 7.08 (s, 1 H, H7), 4.37 (t, J = 129.3 (CH), 129.2 (CH), 125.3 (Cq), 124.6 (CH),
6.5 Hz, 2 H, H5), 3.86 (s, 3 H, OMe), 3.72 (s, 3 H, 122.6 (Cq), 119.2 (Cq), 116.3 (Cq), 111.3 (CH),
OMe), 3.32 (s, 3 H, OMe), 3.07 (t, J = 6.5 Hz, 2 H, 110.8 (CH), 55.8 (2 CH3), 51.9 (CH3), 43.2
H6) (CH2), 28.0 (CH2)
5g
3000, 2957, 2834, 1701,
1552, 1496, 1474, 1356,
1263, 1217, 1137, 1116,
1078, 1044, 1015
8.57 (dd, J = 1.7, 4.9 Hz, 1 H, H4¢), 8.47 (dd, J = 0.7, 160.3 (Cq), 150.5 (Cq), 149.8 (Cq), 148.6 (Cq),
2.2 Hz, 1 H, H2¢), 7.73 (ddd, J = 1.7, 2.2, 7.8 Hz, 1 147.2 (Cq), 137.3 (CH), 131.6 (CH), 129.1 (CH),
H, H5¢), 7.43 (ddd, J = 0.7, 4.9, 7.8 Hz, 1 H,
128.9 (Cq), 128.3 (Cq), 124.2 (Cq), 122.9 (Cq),
H6¢),7.34 (s, 1 H, H10), 7.07 (s, 1 H, H7), 4.50 (t, J = 119.3 (Cq), 116.3 (CH), 111.4 (Cq), 110.6 (Cq),
6.5 Hz, 2 H, H5), 3.72 (s, 3 H, OMe), 3.51 (s, 3 H,
OMe), 3.34 (s, 3 H, OMe), 3.07 (t, J = 6.5 Hz, 2 H,
H6)
55.9 (2 CH3), 51.8 (CH3), 43.2 (CH2), 28.0 (CH2)
5h
2952, 1710, 1612, 1506,
1441, 1354, 1261, 1245,
1215, 1198, 1174, 1135,
1070, 1008
7.47 (d, J = 7.5 Hz, 2 H, H2Bn, H6Bn), 7.40 (t, J = 7.5 161.5 (Cq), 158.4 (Cq), 150.2 (Cq), 147.9 (Cq),
Hz, 2 H, H3Bn, H5Bn), 7.36 (s, 1 H, H10), 7.34 (t, J = 136.9 (Cq), 130.9 (2 CH), 130.7 (Cq), 128.6 (2
7.5 Hz, 1 H, H4Bn), 7.22 (d, J = 8.8 Hz, 2 H, H2¢,
H6¢), 7.00 (d, J = 8.8 Hz, 2 H, H3¢, H5¢), 6.78 (s, 1 H, CH), 127.1 (Cq), 124.5 (Cq), 118.4 (Cq), 117.3
H7), 5.10 (s, 2 H, OCH2), 4.56 (t, J = 6.7 Hz, 2 H, (Cq), 114.0 (2 CH), 110.5 (CH), 109.9 (CH), 70.0
H5), 3.94 (s, 3 H, OMe), 3.87 (s, 3 H, OMe), 3.56 (s, (CH2), 56.2 (CH3), 56.0 (CH3), 51.4 (CH3), 43.0
3 H, OMe), 3.04 (t, J = 6.7 Hz, 2 H, H6) (CH2), 28.8 (CH2)
CH), 128.4 (Cq),128.0 (CH), 127.7 (Cq), 127.6 (2
Synthesis 2009, No. 24, 4149–4158 © Thieme Stuttgart · New York

4156
J. Tóth et al.
PAPER
Table 3 Spectral Data of Compounds 5 Prepared (continued)
Product IR (KBr, cm–1) 1H NMRa (CDCl3, TMS) d, J (Hz)
8.16 (s, 1 H, H2¢), 7.92 (t, J = 7.3 Hz, 1 H, H5¢), 7.79 187.2 (Cq), 150.6 (Cq), 147.2 (Cq), 146.9 (Cq),
13C NMR (CDCl3,TMS) d
5i
2937, 1705, 1630, 1569,
1520, 1499, 1349, 1264,
1216, 1178, 1147, 1133,
1093, 1004
(d, J = 7.3 Hz, 1 H, H4¢), 7.62 (t, J = 8.5 Hz, 1 H, 137.6 (CH), 137.1 (Cq), 133.6 (Cq), 132.9 (CH),
H4¢¢), 7.59 (d, J = 8.5 Hz, 2 H, H2¢¢, H6¢¢), 7.52 (d, 129.6 (2 CH), 129.4 (CH), 129.3 (Cq), 128.8 (Cq),
J = 8.5 Hz, 2 H, H3¢¢, H5¢¢), 7.45 (s, 1 H, H10), 7.41 128.7 (Cq), 128.1 (2 CH), 127.7 (Cq), 125.3 (CH),
(d, J = 7.3 Hz, 1 H, H6¢), 7.10 (s, 1 H, H7), 4.27 (t, 124.4 (Cq), 122.4 (CH), 116.4 (Cq), 111.5 (CH),
J = 6.1 Hz, 2 H, H5), 3.87 (s, 3 H, OMe), 3.65 (s, 3 110.8 (CH), 55.9 (CH3), 55.8 (CH3), 43.3 (CH2),
H, OMe), 3.10 (t, J = 6.1 Hz, 2 H, H6)
28.2 (CH2)
5j
2939, 1627, 1500, 1468,
1431, 1411, 1390, 1353,
1265, 1214, 1147, 1084,
1013
7.51 (d, J = 7.4 Hz, 2 H, H2¢¢, H6¢¢), 7.43 (s, 1 H,
187.9 (Cq), 150.4 (Cq), 147.9 (Cq), 137.5 (Cq),
H10), 7.33 (t, J = 7.4 Hz, 1 H, H4¢¢), 7.14 (t, J = 7.4 133.7 (Cq), 132.7 (q, CH), 131.7 (2 CH), 131.2
Hz, 2 H, H3¢¢, H5¢¢), 7.02 (s, 4 H, HAr2), 6.80 (s, 1 H, (Cq), 129.6 (Cq), 129.5 (2 CH), 128.0 (Cq), 127.9
H7), 4.35 (t, J = 6.5 Hz, 2 H, H5), 3.95 (s, 3 H,
(2 CH), 127.8 (2 CH), 126.9 (Cq), 126.3 (Cq),
OMe), 3.89 (s, 3 H, OMe), 3.08 (t, J = 6.5 Hz, 2 H, 117.0 (Cq), 110.6 (CH), 110.0 (CH), 56.2 (CH3),
H6)
56.0 (CH3), 43.2 (CH2), 28.9 (CH2)
5k
2938, 2836, 1677, 1645,
1550, 1500, 1468, 1450,
1356, 1267, 1236, 1216,
1147, 1092, 1055, 1036,
1016
7.57 (m, 3 H, HPh, H10), 7.26 (t, J = 7.4 Hz, 1 H,
187.7 (Cq), 150.4 (Cq), 147.7 (Cq), 137.8 (Cq),
H5¢), 7.14 (m, 3 H, HPh), 6.98 (m, 2 H, H3¢, H6¢), 6.92 134.3 (Cq), 132.5 (CH), 132.2 (CH), 131.8 (Cq),
(t, J = 7.4 Hz, 1 H, H4¢), 6.81 (s, 1 H, H7), 4.44 (m, 131.1 (Cq), 129.2 (2 CH), 129.1 (CH), 128.9
1 H, H5), 4.33 (m, 1 H, H5), 3.95 (s, 3 H, OMe), 3.90 (CH), 128.4 (Cq), 128.3 (Cq), 127.7 (2 CH), 127.1
(s, 3 H, OMe), 3.10 (t, J = 6.7 Hz, 2 H, H6)
(Cq), 126.1 (CH), 124.9 (Cq), 117.1 (Cq), 110.6
(CH), 110.5 (CH), 56.2 (CH3), 56.0 (CH3), 43.3
(CH2), 29.0 (CH2)
5l
3004, 2935, 2839, 1630,
1597, 1505, 1471, 1443,
1429, 1409, 1394, 1353,
1321, 1281, 1258, 1214,
1167, 1142, 1084, 1035,
1016
7.55 (d, J = 7.0 Hz, 2 H, H2¢¢, H6¢¢), 7.48 (s, 1 H,
185.5 (Cq), 163.2 (Cq), 150.1 (Cq), 147.8 (Cq),
H10), 7.10 (m, 5 H, HPh), 6.78 (s, 1 H, H7), 6.60 (d, 132.1 (2 CH), 131.2 (Cq), 130.8 (Cq), 130.4 (Cq),
J = 7.0 Hz, 2 H, H3¢¢, H5¢¢), 4.26 (t, J = 6.8 Hz, 2 H, 130.3 (2 CH), 130.2 (Cq), 127.8 (CH), 127.7 (2
H5), 3.94 (s, 3 H, OMe), 3.90 (s, 3 H, OMe), 3.73 (s, CH), 127.5 (Cq), 127.0 (Cq), 126.3 (Cq), 117.4
3 H, OMe), 3.06 (t, J = 6.8 Hz, 2 H, H6)
(Cq), 113.1 (2 CH), 110.6 (CH), 109.8 (CH), 56.1
(CH3), 55.9 (CH3), 55.3 (CH3), 43.0 (CH2), 29.0
(CH2)
5m
5n
3022, 2964, 2840, 1628,
1601, 1574, 1504, 1473,
1423, 1351, 1256, 1214,
1170, 1143, 1113, 1091,
1080, 1027
7.53 (d, J = 8.9 Hz, 2 H, H2¢¢, H6¢¢), 7.47 (s, 1 H,
186.3 (Cq), 163.6 (Cq), 150.3 (Cq), 147.9
H10), 7.07 (s, 4 H, HAr2), 6.79 (s, 1 H, H7), 6.64 (d, (Cq),133.6 (Cq), 132.1 (2 CH), 131.6 (2 CH),
J = 8.9 Hz, 2 H, H3¢¢, H5¢¢), 4.26 (t, J = 6.5 Hz, 2 H, 130.8 (Cq), 130.7 (Cq), 130.0 (Cq), 129.9 (Cq),
H5), 3.95 (s, 3 H, OMe), 3.90 (s, 3 H, OMe), 3.78 (s, 127.9 (2 CH), 127.8 (Cq), 127.2 (Cq), 125.0 (Cq),
3 H, OMe), 3.06 (t, J = 6.5 Hz, 2 H, H6)
117.2 (Cq), 113.4 (2 CH), 110.6 (CH), 110.0
(CH), 56.2 (CH3), 56.0 (CH3), 55.5 (CH3), 43.1
(CH2), 29.0 (CH2)
2936, 2840, 1629, 1599,
1573, 1505, 1469, 1369,
1265, 1217, 1167, 1145,
1030, 1014
7.61 (s, 1 H, H10), 7.58 (d, J = 8.8 Hz, 2 H, H2¢¢,
185.9 (Cq), 163.6 (Cq), 150.4 (Cq), 147.7 (Cq),
H6¢¢), 6.96 (s, 2 H, H3¢, H6¢), 6.80 (s, 1 H, H7), 6.68 135.2 (Cq), 134.2 (Cq), 132.9 (CH), 131.7 (2 CH),
(d, J = 8.8 Hz, 2 H, H3¢¢, H5¢¢), 4.36 (m, 1 H, H5),
131.6 (Cq), 130.9 (Cq), 130.3 (Cq), 130.1 (Cq),
4.22 (m, 1 H, H5), 3.95 (s, 3 H, OMe), 3.90 (s, 3 H, 128.9 (CH), 128.2 (Cq), 127.6 (Cq), 126.5 (Cq),
OMe), 3.78 (s, 3 H, OMe), 3.07 (t, J = 6.8 Hz, 2 H, 122.5 (Cq), 117.1 (Cq), 113.3 (2 CH), 110.7 (CH),
H6)
110.5 (CH), 56.2 (CH3), 56.0 (CH3), 55.5 (CH3),
43.3 (CH2), 29.0 (CH2)
5o
5p
3008, 2941, 2833, 1625,
1609, 1586, 1508, 1466,
1440, 1411, 1354, 1322,
1281, 1261, 1214, 1195,
1171, 1143, 1084, 1068,
1011
7.41 (s, 1 H, H10), 7.35 (d, J = 8.3 Hz, 2 H, H2¢¢,
186.8 (Cq), 150.4 (Cq), 147.9 (Cq), 136.4 (Cq),
H6¢¢), 7.20 (d, J = 8.3 Hz, 2 H, H3¢¢, H5¢¢), 7.08 (m, 131.2 (Cq), 130.95 (2 CH), 130.9 (3 CH), 130.8
5 H, HPh), 6.81 (s, 1 H, H7), 4.36 (t, J = 6.0 Hz, 2 H, (Cq), 130.4 (2 CH), 128.0 (Cq), 127.9 (Cq), 127.8
H5), 3.95 (s, 3 H, OMe), 3.89 (s, 3 H, OMe), 3.08 (t, (Cq), 127.7 (2 CH), 127.4 (Cq), 126.3 (Cq), 117.0
J = 6.0 Hz, 2 H, H6)
(Cq), 110.6 (CH), 109.8 (CH), 56.1 (CH3), 56.0
(CH3), 43.1 (CH2), 28.9 (CH2)
3010, 2943, 1633, 1586,
1502, 1471, 1442, 1405,
1355, 1261, 1218, 1148,
1095, 1068, 1056, 1014
7.54 (s, 1 H, H10), 7.41 (d, J = 8.4 Hz, 2 H, H2¢¢,
186.6 (Cq), 150.6 (Cq), 147.8 (Cq), 136.7 (Cq),
H6¢¢), 7.25 (d, J = 8.4 Hz, 2 H, H3¢¢, H5¢¢), 7.19 (d, 134.3 (Cq), 133.1 (Cq), 132.3 (CH), 132.2 (Cq),
J = 7.9 Hz, 1 H, H6¢), 7.07 (t, J = 7.9 Hz, 1 H, H5¢), 131.0 (Cq), 130.9 (2 CH), 130.5 (2 CH), 129.3
6.97 (d, J = 7.9 Hz, 1 H, H3¢), 6.95 (d, J = 7.9 Hz, 1 (CH), 129.1 (CH), 128.3 (Cq), 127.5 (Cq), 126.7
H, H4¢), 6.81 (s, 1 H, H7), 4.45 (m, 1 H, H5), 4.34 (m, (Cq), 126.3 (CH), 125.3 (Cq), 117.0 (Cq), 110.6
1 H, H5), 3.96 (s, 3 H, OMe), 3.90 (s, 3 H, OMe),
3.10 (m, 2 H, H6)
(CH), 110.5 (CH), 56.2 (CH3), 56.0 (CH3), 43.3
(CH2), 29.0 (CH2)
Synthesis 2009, No. 24, 4149–4158 © Thieme Stuttgart · New York

PAPER
Oxidation of Substituted Pyrrolidines by N-Bromosuccinimide
1H NMRa (CDCl3, TMS) d, J (Hz) 13C NMR (CDCl3,TMS) d
4157
Table 3 Spectral Data of Compounds 5 Prepared (continued)
Product IR (KBr, cm–1)
5q 2877, 1633, 1584, 1502,
7.39 (s, 1 H, H10), 7.36 (d, J = 8.5 Hz, 2 H, H2¢¢,
186.9 (Cq), 150.4 (Cq), 147.9 (Cq), 147.4 (Cq),
1431, 1354, 1259, 1171,
1139, 1066, 1041, 1010
H6¢¢), 7.29 (d, J = 8.5 Hz, 2 H, H3¢¢, H5¢¢), 6.80 (s, 1 147.0 (Cq), 136.7 (Cq), 131.2 (Cq), 130.9 (2 CH),
H, H7), 6.52 (s, 2 H, H2¢, H5¢), 5.87 (s, 2 H, OCH2O), 130.8 (2 CH), 128.0 (Cq), 127.7 (Cq), 127.2 (Cq),
4.37 (t, J = 6.6 Hz, 2 H, H5), 3.95 (s, 3 H, OMe), 3.89 126.4 (Cq), 124.5 (Cq), 124.3 (Cq), 117.0 (Cq),
(s, 3 H, OMe), 3.08 (t, J = 6.6 Hz, 2 H, H6)
111.0 (CH), 110.6 (CH), 109.8 (CH), 107.8
(CH), 101.1 (CH2), 56.1 (CH3), 56.0 (CH3), 43.0
(CH2), 28.9 (CH2)
a Aryl groups at C2 are indicated using ¢, while those at C3 are indicated by ¢¢.
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Acknowledgment
This work was financially supported by the National Fund for Sci-
ence and Research, Hungary (OTKA Project No. T 046196). A
grant from EGIS Pharmaceuticals provided to J.T. is gratefully ap-
preciated.
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